Proposed Framework for Evaluating the Safety of Dietary Supplements -- For Comment

FOR COMMENT......Page 1
Copyright......Page 2
Foreword......Page 9
Contents......Page 11
THE COMMITTEE'S TASK......Page 13
BACKGROUND......Page 14
FINDINGS......Page 15
Step One: Screening/Flagging......Page 17
Scoring and Sorting the Data......Page 20
Step Three: Critical Safety Evaluation......Page 21
Guiding Principles to Follow in Evaluating Data in the Framework......Page 22
Attributes of the Proposed Framework......Page 23
SECOND PHASE OF THIS STUDY......Page 24
1 Introduction and Background......Page 25
GENERAL BACKGROUND INFORMATION ABOUT DIETARY SUPPLEMENTS......Page 26
Consumer Expectations About Dietary Supplement Safety......Page 27
History of the Federal Regulation of Dietary Supplements......Page 28
Federal Food, Drug, and Cosmetic Act of 1938......Page 29
Early Attempts to Regulate the Industry......Page 30
1976 Proxmire Amendments......Page 31
The Dietary Supplement and Health Education Act......Page 32
Good Manufacturing Practices......Page 36
REFERENCES......Page 37
OTHER APPROACHES FOR CONSIDERING DIETARY SUPPLEMENT SAFETY......Page 41
U.S. Pharmacopeia-National Formulary......Page 43
American Herbal Pharmacopoeia......Page 44
Commission E......Page 45
The Physician's Desk Reference for Herbal Medicines and the Physician's Desk Reference for…......Page 46
ANALYSIS OF DIFFERENT APPROACHES TO DIETARY SUPPLEMENT EVALUATION......Page 47
ATTRIBUTES OF AN IDEAL FRAMEWORK FOR EVALUATING DIETARY SUPPLEMENTS......Page 48
REFERENCES......Page 50
Ingredients versus Products......Page 51
Initiation of the Process......Page 53
Evaluation and Weighting of Available Information......Page 56
Monograph Preparation, Internal Review, and In-Depth Safety Evaluation......Page 57
REFERENCES......Page 58
DESCRIPTION AND USE OF KEY FACTORS......Page 59
Clinical Trials......Page 62
Observational Epidemiological Research......Page 63
Non-Study Information: Historical Use......Page 64
Use of Human Data in the Screening/Flagging and Priority-Setting Steps......Page 67
Use of Human Data in the Critical Safety Evaluation Step......Page 68
Key Factor: Animal Data......Page 69
Extrapolations from Animal Studies......Page 72
Use of Animal Data in the Priority-Setting Step......Page 73
Use of Animal Data in the Critical Safety Evaluation Step......Page 74
Systematically Considering Biological Activity of Structurally Related Substances......Page 75
Considering the Chemical Composition of Botanical Ingredients......Page 76
Use of Bioactivity of Related Substances in the Critical Safety Evaluation Step......Page 77
Key Factor: In Vitro Data......Page 78
Use of In Vitro Data in the Priority Setting Process......Page 79
Prevalence of Use in the Population......Page 80
Use by Vulnerable Subpopulations......Page 82
New Ingredient Status......Page 84
REFERENCES......Page 85
GENERAL APPROACH......Page 89
STEP ONE: SCREENING/FLAGGING......Page 90
Human Data......Page 91
STEP TWO: PRIORITY-SETTING PROCESS......Page 92
General Description of How to Score Information......Page 93
Which Scores Indicate Higher Priority......Page 94
Ranking Ingredients Within the Matrix: Using Scores to Sort Ingredients Into Priority Groups......Page 95
Scoring Human Data......Page 97
Scoring Animal Data......Page 98
Scoring Data on the Biological Activity of Structurally Related and Taxonomically Related Substances......Page 99
Scoring In Vitro Data......Page 100
REFERENCES......Page 101
STEP 3A: DRAFT MONOGRAPH PREPARATION AND REVIEW BY THE FOOD AND DRUG ADMINISTRATION......Page 103
STEP 3B: CRITICAL EVALUATION BY AN EXTERNAL ADVISORY COMMITTEE......Page 106
Preparation of Draft Monographs......Page 108
Management of the External Advisory Committee......Page 109
SUMMARY......Page 110
ATTRIBUTES OF THE PROPOSED FRAMEWORK......Page 111
LIMITATIONS OF THE PROPOSED FRAMEWORK......Page 112
SUMMARY......Page 113
CHOICE OF INGREDIENTS FOR PROTOTYPE MONOGRAPH DEVELOPMENT......Page 115
REFERENCES......Page 116
AGENCY FOR HEALTHCARE RESEARCH AND QUALITY......Page 118
U.S. PHARMACOPEIA-NATIONAL FORMULARY......Page 119
AMERICAN HERBAL PHARMACOPOEIA......Page 120
AMERICAN HERBAL PRODUCTS ASSOCIATION......Page 121
NATURAL MEDICINES COMPREHENSIVE DATABASE......Page 122
COMMISSION E......Page 123
HEALTH CANADA NATURAL HEALTH PRODUCTS DIRECTORATE......Page 125
REFERENCES......Page 126
PREMARKET APPROVAL OF FOOD ADDITIVES......Page 128
SELECT COMMITTEE ON GRAS SUBSTANCES......Page 129
COSMETICS INGREDIENT REVIEW......Page 130
NEW DRUGS......Page 131
OVER-THE-COUNTER DRUGS......Page 132
NEW CHEMICALS PROGRAM......Page 133
TOLERABLE UPPER INTAKE LEVEL MODEL FOR NUTRIENTS......Page 134
REFERENCES......Page 135
Appendix C Possible Combinations of Scores......Page 136
Appendix D Table of Food and Drug Administration Actions on Dietary Supplements......Page 150
Appendix E Presenters at the Open Sessions of the Project on the Framework for Evaluating the.........Page 152
Appendix F Biographical Sketches of Committee Members......Page 153